Arsenic Nanoparticles Trigger Apoptosis via Anoikis Induction in OECM-1 Cells.
Alejandra A CovarrubiasMauricio Reyna-JeldesSeidy Pedroso SantanaSabrina MarínCarolina Madero-MendozaCecilia DemergassoClaudio CoddouPublished in: International journal of molecular sciences (2024)
Arsenic compounds have been used as therapeutic alternatives for several diseases including cancer. In the following work, we obtained arsenic nanoparticles (AsNPs) produced by an anaerobic bacterium from the Salar de Ascotán , in northern Chile, and evaluated their effects on the human oral squamous carcinoma cell line OECM-1. Resazurin reduction assays were carried out on these cells using 1-100 µM of AsNPs, finding a concentration-dependent reduction in cell viability that was not observed for the non-tumoral gastric mucosa-derived cell line GES-1. To establish if these effects were associated with apoptosis induction, markers like Bcl2, Bax, and cleaved caspase 3 were analyzed via Western blot, executor caspases 3/7 via luminometry, and DNA fragmentation was analyzed by TUNEL assay, using 100 µM cisplatin as a positive control. OECM-1 cells treated with AsNPs showed an induction of both extrinsic and intrinsic apoptotic pathways, which can be explained by a significant decrease in P-Akt/Akt and P-ERK/ERK relative protein ratios, and an increase in both PTEN and p53 mRNA levels and Bit-1 relative protein levels. These results suggest a prospective mechanism of action for AsNPs that involves a potential interaction with extracellular matrix (ECM) components that reduces cell attachment and subsequently triggers anoikis , an anchorage-dependent type of apoptosis.
Keyphrases
- cell cycle arrest
- induced apoptosis
- pi k akt
- cell death
- signaling pathway
- endoplasmic reticulum stress
- oxidative stress
- cell proliferation
- extracellular matrix
- drinking water
- heavy metals
- squamous cell carcinoma
- microbial community
- binding protein
- single cell
- bone marrow
- circulating tumor
- south africa
- amino acid
- small molecule
- mesenchymal stem cells
- papillary thyroid
- protein protein
- lymph node metastasis
- cell free